Dose Escalation Study of Teclistamab, a Humanized BCMA*CD3 Bispecific Antibody, in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-1)

• ClinicalTrials.gov Identifier: NCT03145181
• Recruitment Status: Recruiting
• First Posted: May 9, 2017
• Last Update Posted: April 25, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: April 28, 2017
• First Posted Date: May 9, 2017
• Last Update Posted Date: April 25, 2024
• Actual Study Start Date: May 16, 2017
• Actual Primary Completion Date: November 9, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 4, 2021)

• Dose Limiting Toxicity (DLT) [ Time Frame: Up to Day 28 ]
  The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and defined as any of the following events: hematological / non hematological toxicity of Grade 3 or higher.
• Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: Up to 7 years and 3 months ]
  An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

Original Primary Outcome Measures (submitted: May 8, 2017)

• Dose Limiting Toxicity (DLT) [ Time Frame: Up to Day 28 ]
  The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and defined as any of the following events: hematological / non hematological toxicity of Grade 3 or higher.
• Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: From signing of Informed Consent Form (ICF) up to follow up (approximately up to 6 months) ]
  An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

Current Secondary Outcome Measures (submitted: November 20, 2020)

• Teclistamab Serum Concentrations [ Time Frame: Up to 8 weeks ]
  Concentration assessment will be done to evaluate the effect of Teclistamab.
• Number of Participants with Teclistamab Antibodies [ Time Frame: Up to 8 weeks ]
  Antibodies to Teclistamab will be assessed to evaluate potential immunogenicity.
• Preliminary Antitumor Activity of Teclistamab at the RP2D(s) in Part 2 [ Time Frame: Up to End of Treatment (Approximately 91 days) ]
  Preliminary antitumor activity of Teclistamab will be done using the International Myeloma Working Group (IMWG) response criteria.
• Biomarker Assessment [ Time Frame: Up to 8 weeks ]
  Biomarker assessment may be done to evaluate the effect of Teclistamab.

Original Secondary Outcome Measures (submitted: May 8, 2017)

• JNJ-64007957 Serum Concentrations [ Time Frame: Up to 8 weeks ]
  Concentration assessment will be done to evaluate the effect of JNJ-64007957.
• Number of Participants with JNJ-64007957 Antibodies [ Time Frame: Up to 8 weeks ]
  Antibodies to JNJ-64007957 will be assessed to evaluate potential immunogenicity.
• Preliminary Antitumor Activity of JNJ-64007957 at the RP2D(s) in Part 2 [ Time Frame: Up to End of Treatment (Approximately 91 days) ]
  Preliminary antitumor activity of JNJ-64007957 will be done using the International Myeloma Working Group (IMWG) response criteria.
• Biomarker Assessment [ Time Frame: Up to 8 weeks ]
  Biomarker assessment may be done to evaluate the effect of JNJ-64007957.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dose Escalation Study of Teclistamab, a Humanized BCMA*CD3 Bispecific Antibody, in Participants With Relapsed or Refractory Multiple Myeloma
• Official Title: A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of Teclistamab, a Humanized BCMA x CD3 Bispecific Antibody in Subjects With Relapsed or Refractory Multiple Myeloma
• Brief Summary: The purpose of this study is to identify the recommended Phase 2 dose(s) (RP2Ds) and schedule assessed to be safe for Teclistamab and to characterize the safety and tolerability of Teclistamab at the RP2Ds.
• Detailed Description: The study will be conducted in 2 parts, separately for IV and SC administration: dose escalation (Part 1) and dose expansion (Part 2). It will evaluate safety, tolerability, pharmacokinetics and preliminary antitumor activity of Teclistamab administered to adult participants with relapsed or refractory multiple myeloma. The overall safety of the study drug will be assessed by physical examinations, Eastern Cooperative Oncology Group performance status, laboratory tests, vital signs, electrocardiograms, adverse event monitoring, and concomitant medication usage. Disease evaluations will include peripheral blood and bone marrow assessments at screening (performed within 28 days) and to confirm stringent complete response (sCR), complete response (CR), or relapse from CR. The end of study (study completion) is defined as 2 years after the last participant in Part 3 has received his or her initial dose of teclistamab. Study record NCT04557098 is Phase 2 part of this study and study record NCT03145181 is Phase 1 part of this study.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hematological Malignancies

Intervention

• Drug: Teclistamab (IV)
  Participants will receive IV infusion of Teclistamab.
  Other Name: JNJ-64007957
• Drug: Teclistamab(SC)
  Participants will receive SC injection of Teclistamab.
  Other Name: JNJ-64007957

Study Arms

• Experimental: Part 1: Dose Escalation (IV)
  Participants will receive Teclistamab intravenously (IV).
  Intervention: Drug: Teclistamab (IV)
• Experimental: Part 2: Dose Expansion (IV)
  Participants will receive Teclistamab IV.
  Intervention: Drug: Teclistamab (IV)
• Experimental: Part 1: Dose Escalation (SC)
  Participants will receive Teclistamab subcutaneously (SC).
  Intervention: Drug: Teclistamab(SC)
• Experimental: Part 2: Dose Expansion (SC)
  Participants will receive Teclistamab SC.
  Intervention: Drug: Teclistamab(SC)

Publications *

• Girgis S, Lin SXW, Pillarisetti K, Banerjee A, Stephenson T, Ma X, Shetty S, Yang TY, Hilder BW, Jiao Q, Hanna B, Adams HC 3rd, Sun YN, Sharma A, Smit J, Infante JR, Goldberg JD, Elsayed Y. Translational Modeling Predicts Efficacious Therapeutic Dosing Range of Teclistamab for Multiple Myeloma. Target Oncol. 2022 Jul;17(4):433-439. doi: 10.1007/s11523-022-00893-y. Epub 2022 Jun 24. Erratum In: Target Oncol. 2022 Aug 1;:
• Moreau P, Garfall AL, van de Donk NWCJ, Nahi H, San-Miguel JF, Oriol A, Nooka AK, Martin T, Rosinol L, Chari A, Karlin L, Benboubker L, Mateos MV, Bahlis N, Popat R, Besemer B, Martinez-Lopez J, Sidana S, Delforge M, Pei L, Trancucci D, Verona R, Girgis S, Lin SXW, Olyslager Y, Jaffe M, Uhlar C, Stephenson T, Van Rampelbergh R, Banerjee A, Goldberg JD, Kobos R, Krishnan A, Usmani SZ. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2022 Aug 11;387(6):495-505. doi: 10.1056/NEJMoa2203478. Epub 2022 Jun 5.
• Usmani SZ, Garfall AL, van de Donk NWCJ, Nahi H, San-Miguel JF, Oriol A, Rosinol L, Chari A, Bhutani M, Karlin L, Benboubker L, Pei L, Verona R, Girgis S, Stephenson T, Elsayed Y, Infante J, Goldberg JD, Banerjee A, Mateos MV, Krishnan A. Teclistamab, a B-cell maturation antigen x CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study. Lancet. 2021 Aug 21;398(10301):665-674. doi: 10.1016/S0140-6736(21)01338-6. Epub 2021 Aug 10.
• Pillarisetti K, Powers G, Luistro L, Babich A, Baldwin E, Li Y, Zhang X, Mendonca M, Majewski N, Nanjunda R, Chin D, Packman K, Elsayed Y, Attar R, Gaudet F. Teclistamab is an active T cell-redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma. Blood Adv. 2020 Sep 22;4(18):4538-4549. doi: 10.1182/bloodadvances.2020002393.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 14, 2022): 282
• Original Estimated Enrollment (submitted: May 8, 2017): 60
• Estimated Study Completion Date: July 22, 2026
• Actual Primary Completion Date: November 9, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Documented diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
• Measurable multiple myeloma that is relapsed or refractory to established therapies with known clinical benefit in relapsed/refractory multiple myeloma or be intolerant of those established multiple myeloma therapies, and a candidate for Teclistamab treatment in the opinion of the treating physician. Prior lines of therapy must include a proteasome inhibitor, an immunomodulatory drug and anti-CD38 monoclonal antibody in any order during the course of treatment. Participants who could not tolerate a proteasome inhibitor or immunomodulatory drugs and an anti-CD38 monoclonal antibody are allowed
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Female participants of childbearing potential must use acceptable method of contraception
• Participants must sign an ICF indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the participant's disease

Exclusion Criteria:

• Prior treatment with any B cell maturation antigen (BCMA) targeted therapy
• Prior antitumor therapy as follows, before the first dose of study drug: Targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less; Monoclonal antibody treatment for multiple myeloma within 21 days; Cytotoxic therapy within 21 days; Proteasome inhibitor therapy within 14 days; Immunomodulatory agent therapy within 7 days; Gene modified adoptive cell therapy (example, chimeric antigen receptor modified T cells, natural killer [NK] cells) within 3 months; Radiotherapy within 14 days or focal radiation within 7 days
• Toxicities from previous anticancer therapies that have not resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
• Received a cumulative dose of corticosteroids equivalent to >= 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)
• Known active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

• Listed Location Countries: France, Netherlands, Spain, Sweden, United States
• Removed Location Countries: Belgium

Administrative Information

• NCT Number: NCT03145181
• Other Study ID Numbers: CR108206; 2016-002122-36 ( EudraCT Number ); 64007957MMY1001 ( Other Identifier: Janssen Research & Development, LLC ); 2023-503438-40-00 ( Registry Identifier: EUCT number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024